Chronic
neuroinflammation is being recognized as a key etiopathological factor in the
development of IOP-independent degeneration of retinal ganglion cells (RGCs) in
glaucoma. Recent studies have highlighted neuroinflammation as a central
pathological process driving RGC damage and disease progression.
Chronic low-grade retinal inflammation in glaucoma activates microglia, recruits peripheral immune cells and induces sustained release of pro-inflammatory cytokines, forming a vicious cycle of inflammation-oxidative stress-cell death that exacerbates neuronal injury.
As resident immune cells in the retina, microglia play a dual role in maintaining retinal homeostasis and responding to stress. Their dynamic functional state critically influences neuronal activities. Under pathological stimuli such as elevated IOP, ischemia, hypoxia or metabolic stress, microglia polarize from a resting state toward the pro- inflammatory M1 phenotype, releasing tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase and excessive reactive oxygen species (ROS), directly inducing RGC apoptosis.
Importantly,
even after IOP normalization, persistently activated M1 microglia maintain an
inflammatory environment, driving irreversible neurodegeneration.
Therefore,
targeted modulation of microglial polarization has been considered a promising
strategy for neuroprotection in glaucoma. However, safe, sustained and precise
neuroprotective modulation of the retinal inflammatory microenvironment remains
a significant challenge.
Plant-derived
exosomes have recently emerged as natural nanovesicles with broad therapeutic
potential due to their wide availability, excellent biocompatibility,
relatively low production cost and capacity to carry diverse bioactive
molecules, including nucleic acids, proteins, lipids and plant-specific
metabolites.
Ginseng
(Panax ginseng), a traditional medicinal herb, contains active compounds such
as ginsenosides, polysaccharides and miRNAs known for their anti-inflammatory,
antioxidative and immunomodulatory properties.
Scientists have developed an injectable fibrin gel delivery system loaded with ginseng-derived exosomes (GE-fibrin gel, GE-gel) to modulate microglial polarization, reduce retinal inflammation and promote RGC survival.
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| Fibrin based hygrogel delivery system of GE |
In
vitro, GE showed strong antioxidant and anti-apoptotic effects by getting rid
of reactive oxygen species caused by oxidative stress and lowering apoptosis in
R28 cells. Both GE and GE-gel stopped lipopolysaccharide from causing
pro-inflammatory M1 polarization of microglia and increased anti-inflammatory
M2 phenotypic change.
Intravitreal
injection of GE-gel suppressed pro-inflammatory microglial activation,
diminished neuroinflammation and improved the survival of RGCs in a chronic
ocular hypertension rat model.
The
study also showed that GE-gel could promote microglial polarization, change the
immune environment in the retina and protect RGCs functionally over the long
term. This approach may hopefully provide promising solutions for rapid and
effective glaucoma therapy.
REFERENCE:
Zhou
D, Tan D, Peng X, Fang C, Yu Y, Iqbal H, Zhang J, Fu L, Tang L, Zhou X, Zhang
X, Xiao R, Zhu W, Yue L, Liang Y. Ginseng-derived exosomes loaded in fibrin gel
promote retinal ganglion cell survival in glaucoma by exerting
anti-inflammatory effects through modulating microglial polarization. Regen
Biomater. 2026 Jul 10;13:rbag146. doi: 10.1093/rb/rbag146. PMID: 42534522;
PMCID: PMC13420499.
